Hematopoiesis- Martin Flashcards
Pluripotent stem cell becomes
Myeloid stem cell ——> (IFU-E —> proerythroblast) RBC, (CFU-Mega—>Megakatocyte) Platelet, (Monoblast) Monocytes
Lymphoid stem cell ——> B cell, T cell, NK cells
Myeloid stem cells give
- (IFU-E —> proerythroblast) RBC,
- (CFU-Mega—>Megakatocyte) Platelet,
- (Monoblast) Monocytes
- (Myeloblast) N, B, E
Hematopoiesis happens where
- Yolk sac
- Liver + Spleen
- BM
- All over many bones
Marrow stromal compartment
Endothelial - barrier
Adipocytes - energy
Stromal cells - structure
M - remove dead cells
BM young
55% red
25% fat marrow
20% Trabecular bone
BM looks like
Field of flowers
BM elderly
25% red
60% marrow fat
15% trabecular bone
BM elderly with osteoporosis
20% red
70% marrow fat
10% trabecular bone
Cellularity in BM
100-age = % cellularity
SCF
Stem cell factor
= fetal tissues and BM
IL3
Replication and growth hematopoietic progenitor cells (Myeloid cells)
IL6
—> Megakaryocytes and N production
IL2
T-cell growth
IL2 + IL6
B-cell growth
GM-CSF
Leukocytes and reticulocyte formation
G-CSF
Increase N during neutropenia
M- CSF
Increase monocytes and macrophages
EPO
Erythropoietin
Made in kidney
Formation of RBCs (TX for anemia)
TPO
Thrombopoietin
Made in liver
Megakaryocytes and platelet production
Steps in erythropoiesis
- Pronormoblast - pale, large central nucleus
- Basophils normoblast - bluish clumps
- Polychromatic normoblast - checker board nucleus
- Orthochromic normoblast - pink
- Polychromatic erythrocytes = reticulocyte (no nucleus)- blue ribosomes
- Erythrocytes
High reticulocyte
Anemia or some kind of trauma
Supravital dye
For RBCs to see ribosomes
Methylene blue
Granulopoiesis
Chromatin condenses Lubulated nucleus Cells shrink Granules in cytoplasm = N, B, E (all myeloid stem)
Agranulopoiesis
Heterochromatin content increases X granules No lobululation nucleus Cells shrink = Lymphocytes (Lymphoid stem), Monocytes (myeloid stem)
Steps for Granulocytic leukopoiesis for Neutrophil
- Myeloblast : large cyto and nucleus, no granules
- Promeylocyte : Azurophilic granules,
- Myelocyte : slight intention in nucleus, smaller granules and many
- Metamyelocyte : huge deep indentation in nucleus where Golgi is, many granules
- Bands : horseshoe nucleus (if high = left shift)
- Polymorphonuclear N : segmented N
Steps for Granulocytic leukopoiesis for Basophils and eosinophils
Same steps as N
(B = dark granules)
(E = red orange granules)
Neutrophils
Phagocytosis
Release anti microbial chemicals
Eosinophils
Phagocytosis
Anti parasitic and bactericidal activity
Basophils
Secrete histamines and heparin
Immature B and T cells
No granules
1-2 nucleoli
Mature B cells and T cells
BM and Thymus
Plasma cells
Activated by B-cells (in spleen and LNs)
Help T-cells go back to BM
Platelet steps
- Megakaryoblast : large kidney shaped nucleus
- Megakaryocytes: multilobed nucleus, endomitosis (many divisions inside cell)
- Platelets : have some granules
Anemia
Decreased RBC volume (low Hb)
Polycythemia
Increased RBC or HB
Thrombopenia
Thrombocythemia
Decreased platelets
Increased platelets
Leukopenia
Lowed WBCs
Leukocytosis
High WBCs
Lymphocytosis
High lymphocytes
Absolute
Means number of cells is low or high (not dependent on percent)
Mean corpuscular volume
MCV = average RBC volume
MCH
Mean corpuscular hemoglobin
average hemoglobin mass in RBC
MCHC
Concentration of hemoglobin in a given volume
RPI
Reticulocyte production index
Reticulocyte % based on RBC volume
Normal MCV
Low MCV
High MCV
80-100 : Nomocytic anemia
Low : Microcytic anemia (RBC is smaller then lymphocytes)
High : macrocytic anemia (RBC is bigger then lymphocytes)
How to measure MCH
Look at central pallor
MCH normal low and high
Normal central pallor : Normochronic = normal Hb in each RBC
Hypochromic : high central pallor
Hyperchromic : low central pallor
RPI increases when
When O2 demand increases = left shift
Normal WBC
4.8-10.8
Higher Hct and Hb in males, since females have menstruation and lower body mass
HCT is what
Hb x 3 = Hct (+/- 3)
MCV increased seen in
B12 and Folate deficiency
MCV decrease is seen in
Thalassemia : Fe+3 deficiency
Anicocytosis
Variation in size : high RDW (RBC distribution width = many sizes of RBCs seen)
LOW : low MCV, Fe deficiency
HIGH : high MCV : B12, folate deficiency
Poikilocytosis
FYI on examples
Many RBC variation in shape seen
Spherocyte no central pallor = hereditary spherocytosis
Oval, ellipse = Fe def, megoloblastic, thalassemia
Bite cells = G6PD def
FE deficiency anemia is going to show
- Anisocytosis + Poikilocytosis
- Microcytic : low MCV
- Hypochromic : low MCHC + MCH
- Increased RDW
- Low Hct, and low RBCs
High reticulocyte index means
Low means
Large RBC destruction
Low production of RBCs
** do this if you see normal MCV**
If you see Microcytic anemia what do you do
- Serum iron level
- Total Fe binding capacity (TIBC)
- serum ferritin lever
= to know the type of Microcytic anemia
FE deficiency vs thalassemia can be done how
Look at RDW (erythrocytes size distribution)
Marked erythrocytes hyperplasia is what
Low M:E ration (myeloid to erythroid)
RBC loss, high reticulocyte = erythroid hyperplasia in BM
Marked erythrocytes hyperplasia is seen in what
G6PD def Sickle cell B-thalassemia Hereditary sperocytosis Autoimmune hemolytic anemia
Sickle cell and spleen
Autoinfarction of spleen
Megaloblastic hyperplasia you see
Seen when
- MCV high
- hypersegmented N
- Hypercellular BM
= in B12 (vegetarian, gasterectomy) and folate (preg, alcohol) deficiency
Aplastic anemia
- Hypocellular BM (low hematopoiesis )
- Low Reticulocyte index
- Normal MCV
EX : Pancytopenia of all cell lines (from chemo, drugs, autoimmune)
Metastatic carcinoma
BM replaced by metastatic tumor, leukemia
- Normal MVC
- Low RPI
Marrow replacement shows
Leukoerythroblastosis
Nucleates, teardrop RBCs, immature WBCs
Extramedullary hematopoiesis
Occurring in organs not in BM (spleen, liver, LN)
= can show abnormal hematopoiesis
Schistocytes are what and seen when
Fragmented RBCs
= Microangiopathic hemolytic anemia
= thrombocytopenia + anemia
Microangiopathic hemolytic anemia
Schistocytes seen
1. Thrombocytopenia
2. Anemia
(DIC, TTP, HUS)
Bite cells and Heinz bodies are seen when
G6PD deficiency (seen with supravital stain) = oxidative stress from infection, drugs, foods)
Hereditary spherocytosis you see
All RBC have NO central pallor and are small
Microcytic hypochromic anemia
Sickle cell anemia you see
HbS causing sickle cells
Normal person CBC of WBCs
Higher N then Lymphocytes (unless child)
Higher T cells then B cells
Neutropenia causes what
Pyogenic acute Bacterial infection (staph and strep)
= supperative infection
- Tx with steroids
Left shift
Bacteria*
Many band cells (immature N)
Metamyelocyes can be seen in very severe infections = Toxic granulation -» accelerated N maturation
Leukemoid reaction
High WBCs + high N, not due to leukemia , due to infection or drugs with HIGH IL6
- HIGH LAP (leukocyte alkaline phosphatase)
- low blasts
High WBC how do you know I it is leukemia or infection
Measure LAP (high in infection) Measure blasts % (low in infection)
Chronic Myelogenous Leukemia (CML)
High WBC, high blasts myeloid + lymphoid, low LAP
Blasts keep increasing : chronic phase —> accelerated phase —> blast phase
Acute myeloid leukemia (AML)
Blasts accumulate myeloid only*
Thrombocytopenia + anemia
+ neutropenia
= Auer rods seen in blood smear
Inadequate granulopoieses
1. Low granulocytic precursors = drugs, toxins 2. Suppressed hematopoietic stem cells = aplastic anemia = marrow replacement 3. Ineffective hematopoiesis = neutropenia (megaloblastic anemia) 4. Congenital neutropenia
High Destruction RBCs seen in
1. Immunological mediated injury to N = autoimmune, Lupus 2. Splenomegaly: = portal HTN, mild neutropenia 3. Increased peripheral utilization : = overwhelming bacteria or fungal infection
EBV you see what in blood smear
Mononucleosis = atypical T-cells
Chronic Lymphocytic Leukemia (CLL)
Older adults
LA, hepatosplenomegaly
= lymphocytes HIGH
Acute lymphoblastic leukemia (ALL)
HIGH BAST lymphocytes cells
Children
Panocytopenia happens
To see if you have leukemia
Flow cytomety to see if all cells are colonal
Monocytosis is seen
Autoimmune
Atypical bacteria infections
Basophilic seen when
Rare and seen in some leukemia like CML
Eosinophilia seen when
Allergy, parasites
Thrombocytopenia SX
Mucocutaneous bleeding = due to low platelets
1. petechiae : small hemorrhagic spots in skin
2. Ecchymosis : bruising large
<100K avoid organ surgery
<50K surgical bleeding
< 20K spontaneous bleeding
3 causes of thrombocytopenia
- Increased platelet destruction
- Decreased platelet production
- Hyperspenism accumulates platelets